Immune Response of an Oral Phage Cocktail in a Mouse Model of Ethanol-Induced Liver Disease.

Cytolysin-positive () cause more severe alcohol-associated hepatitis, and phages might be used to specifically target these bacteria in a clinical trial. Using a humanized mouse model of ethanol-induced liver disease, the effect of cytolytic phage treatment on the intestinal and liver immune response was evaluated. The observed immune response was predominantly anti-inflammatory and tissue-restoring. Besides, live phages could be readily recovered from the serum, spleen, and liver following oral gavage in ethanol-fed mice. We also isolated 20 new phages from the sewage water; six of them exhibited a relatively broad host range. Taken together, the oral administration of cytolytic phages leads to the translocation of phages to the systemic circulation and appears to be safe, following chronic-binge ethanol administration. A cocktail of three phages covers the majority of tested cytolysin-positive strains and could be tested in a clinical trial.